A decade after the anthrax attacks of 2001, much has changed in the world of bioterrorism -- or has it?

Some individual clinician will be the key player the next time there's a covert bioterrorism attack, like the anthrax episode a decade ago.

Despite a marked increase in resources aimed at detecting and foiling bioterrorism, "it's going to be a practitioner who diagnoses the next covert attempt," according to Larry Bush, MD, of JFK Medical Center in Atlantis, Fla.

Bush should know. He made the initial diagnosis of anthrax inhalation after a confused and feverish Robert Stevens walked into the emergency department on Oct. 2, 2001 -- a diagnosis that kicked state and federal health agencies into high alert and probably saved dozens, if not hundreds, of lives.

Behold the Zebra

"What I saw was a man who -- according to his wife -- drove home 24 hours earlier from North Carolina and now was comatose, on a ventilator, and had meningitis," Bush told MedPage Today.

He and colleagues took spinal fluid from the comatose Stevens and Bush noted a preponderance of white cells, indicating inflammation, as well as the telltale boxcar shape of bacillus cells.

"A bacillus that causes meningitis is very rare," Bush said, and Steven had none of the usual precursors of more common infections, such as head trauma.

Of course, he also had none of the common precursors of inhalational anthrax, such as working with hides or in a lab that deals with the pathogen, and for many doctors that would have been that.

The medical school adage about horses and zebras would have kicked in and the incredibly rare diagnosis of anthrax -- 18 cases in the U.S. in the previous century -- would have been dismissed as a zebra.

But Bush took a different view. "In the worst case, this is anthrax," he thought. "And if it's anthrax, it's bioterrorism until proven different."

He notified health authorities and the rest is history.

Anthrax Timeline

The story as it unfolded:

In September and October 2001, envelopes containing Bacillus anthracis were mailed to two senators -- Patrick Leahy and Thomas Daschle -- and to media outlets in New York City and Boca Raton, Fla.

On Oct. 2, Bush made his famous diagnosis. At the time there were already several undiagnosed cases of cutaneous anthrax.

On Oct. 5, Stevens died and a second employee of the same company, in hospital since Sept. 30 with pneumonia, was diagnosed with inhalational anthrax.

Events began to build from Oct. 9 through 19 -- a period that saw several more diagnoses of cutaneous anthrax, after people handled some of the suspect envelopes. Several postal workers were diagnosed in New Jersey and 28 people were found to have been exposed to anthrax after an envelope was opened in Senator Daschle's Hart Senate Office Building office.

On Oct. 19, the CDC linked the four confirmed cases of anthrax to "intentional delivery of B. anthracis spores through mailed letters or packages" and over the next four days, four postal workers in a District of Columbia mail processing plant were hospitalized with inhalational anthrax. Two later died.

Over the next few days, the CDC recommended antibiotic prophylaxis for thousands of people who had potentially been exposed either in the mail plants or in government buildings.

On Oct. 31, a 61-year-old female hospital stockroom worker in New York City died from inhalational anthrax, although how she was exposed remains a mystery.

The last case occurred on Nov. 16, when a 94-year-old woman in Connecticut was admitted to the hospital with fever, cough, and weakness. She died on Nov. 19 and her exposure was linked to cross-contamination from one or more of the suspect letters.

Was Experience the Best Teacher?

Whether all the lessons of those events have been learned is an open question.

Government officials, understandably, think the answer is yes. In an interview published by the Trust for America's Health, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, argued that "today we are in a much better position" as a result of the broad response to the anthrax attacks.

He cited new bio-containment labs and bioterror research centers of excellence, better procurement for vaccines, drugs, and diagnostics that might be needed, and better coordination among the players.

Those "substantial and wise" investments were aimed at closing what Fauci called the two major gaps that existed a decade ago -- lack of basic and applied research into vaccines, diagnostics, and therapeutics and the absence of "a clear public health response system."

But, after 10 years and "a huge investment" in bioterrorism resources, the tripwire for another attack is still the same as it was, according to David Relman, MD, of Stanford University in Stanford, Calif.

Some "astute clinician" is going to pick up the first signs of any new attack, he told MedPage Today. And the only certainty is that "the next attack will not look like the last."

Are doctors ready for that?

The View from the Trenches

Those in the infectious disease field are highly aware of their role as a "biosensor," according to Peggy Neill, MD, of Brown University in Providence, RI. But for doctors in other fields, consciousness of the issue has "probably somewhat receded," she told MedPage Today.

A challenge, she said, is sustaining "interest and expertise among very different groups of clinicians and I don't think we yet quite have an answer to that."

Investment in new reference labs and in surveillance systems is useful and important, Neill noted. "The testing network is much, much better than it was before," she said.

But the major gap is that it is still not possible to say -- on any given day on a real-time basis -- how many cases of botulism or pneumonia or unexplained rash are in hospitals around the nation, she said.

In a retrospective article in Annals of Internal Medicine, Bush and co-author Maria Perez, MD, also of JFK Medical Center, argued that "many aspects of the 2001 anthrax attacks went well."

Specifically, the pathogen was quickly identified, post-exposure prophylaxis was successfully deployed, rapid diagnosis and multi-disciplinary care reduced mortality compared with historical rates, and both medical personnel and lay volunteers leapt into the breach "during a time of fear and uncertainty."

On the other hand, knowledge about anthrax was outdated and inaccurate, vaccine administration was confused and delayed, and there was considerable hoarding of antibiotics.

Perhaps most important, Bush and Perez argued, established "syndromic surveillance systems" failed to pick up the attack, although several cases already existed by the time Stevens walked into the ER.

Bush told MedPage Today that syndromic surveillance is never going to be enough. By the time the data is collated and someone notices a pattern that indicates bioterrorism, "you're way behind the curve."

Indeed, that sort of surveillance -- environmental detection and observing the response of target populations -- is getting better, according to Relman, "but we're still learning to sort the noise from the true signal."

And the next attack, if there is one, will probably still be first detected by someone on medicine's front lines, rather than watching numbers on a chart, he said.

Another major unsettled issue, Bush said, is who should be in charge. On one hand, a bioterror attack is by definition a medical emergency. On the other, it's a criminal act.

"I can tell you," Bush said, "that in Florida the medical folks were pushed aside by the FBI."

Eventually -- long after the medical response was over -- the criminal investigation led the FBI to the conclusion that a single person was behind the attacks: Bruce Ivins, PhD, a microbiologist at the United States Army Medical Research Institute of Infectious Diseases in Fort Detrick, Md.

Ivins died in 2008, apparently a suicide, after learning that the FBI planned to charge him. No charges were ever brought and there remains significant controversy over whether the FBI got it right.

"The government has decided it was one crazed person and it doesn't go beyond that," Bush said. "I don't know if that's true or not, but if it isn't true haven't we sort of missed the boat?"